Striataldopamine D₂/D₃ receptorsmediateresponseinhibition and relatedactivity in frontostriatalneuralcircuitry in humans.

Departments of Psychiatry and Biobehavioral Sciences and Molecular and Medical Pharmacology, and Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90095, USA.

Abstract

Impulsive behavior is thought to reflect a traitlike characteristic that can have broad consequences for an individual's success and well-being, but its neurobiological basis remains elusive. Although striataldopamine D₂-like receptors have been linked with impulsive behavior and behavioral inhibition in rodents, a role for D₂-like receptor function in frontostriatal circuits mediating inhibitory control in humans has not been shown. We investigated this role in a study of healthy research participants who underwent positron emission tomography with the D₂/D₃ dopamine receptor ligand [¹⁸F]fallypride and BOLD fMRI while they performed the Stop-signal Task, a test of responseinhibition. Striataldopamine D₂/D₃ receptor availability was negatively correlated with speed of responseinhibition (stop-signal reaction time) and positively correlated with inhibition-related fMRI activation in frontostriatalneuralcircuitry. Correlations involving D₂/D₃ receptor availability were strongest in the dorsal regions (caudate and putamen) of the striatum, consistent with findings of animal studies relating dopaminereceptors and responseinhibition. The results suggest that striatal D₂-like receptor function in humans plays a major role in the neuralcircuitry that mediates behavioral control, an ability that is essential for adaptive responding and is compromised in a variety of common neuropsychiatric disorders.

Successful Stop vs. Go fMRI contrast and negative correlation with SSRT. Z-statistic map for Stop vs. Go is represented by hot colors, and negative correlation of Stop vs. Go and SSRT is represented by cool colors. Stop vs. Go activations were found in regions typically reported in fMRI studies of the task, including right inferior frontal gyrus, pre-SMA, anterior cingulate, and the insula (see for list of regions). Clusters corresponding to the negative correlation between Stop vs. Go and SSRT were found in the right caudate, putamen, superior frontal gyrus, and left orbitofrontal cortex (see for full list of regions). No regions showed significant clusters for positive correlation with SSRT. Z-statistic maps were whole-brain, cluster-corrected (voxel height threshold: Z>1.96, cluster-forming threshold: P<0.05). Z-statistic maps are overlaid on the group mean high-resolution anatomical image. Numbers to the side of images represent Z-coordinates in MNI standard space. Images are presented in radiological orientation (right=left).